Skip to main content
SpringerLink
Log in

Insulin resistance, metabolic syndrome and chronic low grade inflammation in Sheehan’s syndrome on standard replacement therapy: a case control study

  • Published:
Pituitary Aims and scope Submit manuscript

Abstract

Background

Increased clustering of metabolic risk factors has been demonstrated in patients with hypopituitarism on standard replacement therapy. This usually has been attributed to persistent growth hormone deficiency, though contribution from underlying etiology of hypopituitarism cannot be underestimated. We, therefore, studied conventional metabolic risk factors and pro inflammatory markers in a cohort of hypopituitary patients in whom the etiology was Sheehan’s syndrome.

Material & Methods

We studied 30 GH naive patients with Sheehan’s syndrome (SS) on standard replacement therapy and compared with healthy age, BMI and parity matched controls. All subjects were normotensive, non-diabetic, non-smokers and none had history of any acute or chronic illness. We recorded height, weight, BMI, waist circumference and waist hip ratio, besides measuring biochemical parameters like lipid profile, fasting plasma glucose and insulin, sVCAM-1, ICAM-1 and hsCRP.

Results

Metabolic syndrome and impaired glucose tolerance were more common with SS patients. Similarly total cholesterol (mean ± SD, 5.21 ± 0.98 vs 4.57 ± 0.88, P = 0.00), LDL-cholesterol (3.15 ± 0.90 vs 2.67 ± 0.75, P = 0.02), triglycerides (2.14 ± 1.00 vs 1.43 ± 0.45, P = 0.00) and pro-inflammatory markers i.e. hsCRP (3.95 ± 2.58 vs 1.45 ± 2.77, P = 0.00) were significantly higher in patients with SS. hsCRP positively correlated with fasting insulin (r = 0.40, P = 0.02), HOMA-IR (r = 0.38, P = 0.03) and negatively with HDL (r = − 0.33, P = 0.05).

Conclusions

GH naïve SS patients on standard replacement therapy have increased clustering of metabolic and pro-inflammatory risk factors.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Veldhuis JD, Hammond JM (1980) Endocrine function after spontaneous infarction of the human pituitary: report, review, and reappraisal. Endocr Rev 1:100–107

    Article  CAS  PubMed  Google Scholar 

  2. De Gennes JL, Turpin G, Heshmati HM, Lebrun A (1979) Hypopituitarism and hyperlipidemia. Protective effect of growth hormone deficiency against atherosclerosis. Ann Endocrinol (Paris) 40:557–558

    Google Scholar 

  3. Rosén T, Bengtsson BA (1990) Premature mortality due to cardiovascular disease in hypopituitarism. Lancet 4:285–288

    Article  Google Scholar 

  4. Bates AS, Van’t Hoff W, Jones PJ, Clayton RN (1996) The effect of hypopituitarism on life expectancy. J Clin Endocrinol Metab 81:1169–1172

    CAS  PubMed  Google Scholar 

  5. Verhelst J, Mattsson AF, Luger A, Thunander M, Góth MI, Koltowska-Häggström M, Abs R (2011) Prevalence and characteristics of the metabolic syndrome in 2479 hypopituitary patients with adult-onset GH deficiency before GH replacement: a KIMS analysis. Eur J Endocrinol 165:881–889

    Article  CAS  PubMed  Google Scholar 

  6. Sesmilo G, Miller KK, Hayden D, Klibanski A (2001) Inflammatory cardiovascular risk markers in women with hypopituitarism. J Clin Endocrinol Metab 86:5774–5781

    Article  CAS  PubMed  Google Scholar 

  7. Beauregard C, Utz AL, Schaub AE, Nachtigall L, Biller BM, Miller KK, Klibanski A (2008) Growth hormone decreases visceral fat and improves cardiovascular risk markers in women with hypopituitarism: a randomized, placebo-controlled study. J Clin Endocrinol Metab 93:2063–2071

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  8. Kelestimur F (2003) Sheehan’s syndrome. Pituitary 6:181–188

    Article  PubMed  Google Scholar 

  9. Zargar AH, Singh B, Laway BA, Masoodi SR, Wani AI, Bashir MI (2005) Epidemiological aspects of postpartum pituitary hypofunction (Sheehan’s syndrome). Fertil Steril 84:523–528

    Article  PubMed  Google Scholar 

  10. Markussis V, Beshyah SA, Fisher C, Sharp P, Nicolaides AN, Johnston DG (1992) Detection of premature atherosclerosis by high-resolution ultrasonography in symptom-free hypopituitary adults. Lancet 340:1188–1192

    Article  CAS  PubMed  Google Scholar 

  11. Bülow B, Hagmar L, Eskilsson J, Erfurth EM (2000) Hypopituitary females have a high incidence of cardiovascular morbidity and an increased prevalence of cardiovascular risk factors. J Clin Endocrinol Metab 85:574–584

    PubMed  Google Scholar 

  12. Capaldo B, Patti L, Oliviero U, Longobardi S, Pardo F, Vitale F, Fazio S, Di Rella F, Biondi B, Lombardi G, Sacca L (1997) Increased arterial intima-media thickness in childhood-onset growth hormone deficiency. J Clin Endocrinol Metab 82:1378–1381

    Article  CAS  PubMed  Google Scholar 

  13. Pfeifer M, Verhovec R, Zizek B, Prezelj J, Poredos P, Clayton RN (1999) Growth hormone (GH) treatment reverses early atherosclerotic changes in GH-deficient adults. J Clin Endocrinol Metab 84:453–457

    CAS  PubMed  Google Scholar 

  14. Evans LM, Davies JS, Goodfellow J, Rees JA, Scanlon MF (1999) Endothelial dysfunction in hypopituitary adults with growth hormone deficiency. Clin Endocrinol (Oxf) 50:457–464

    Article  CAS  Google Scholar 

  15. Van der Klaauw AA, Biermasz NR, Feskens EJ, Bos MB, Smit JW, Roelfsema F, Corssmit EP, Pijl H, Romijn JA, Pereira AM (2007) The prevalence of the metabolic syndrome is increased in patients with GH deficiency, irrespective of long-term substitution with recombinant human GH. Eur J Endocrinol 156:455–462

    Article  PubMed  Google Scholar 

  16. Attanasio AF, Mo D, Erfurth EM, Tan M, Ho KY, Kleinberg D, Zimmermann AG, Chanson P (2010) Prevalence of metabolic syndrome in adult hypopituitary growth hormone (GH)-deficient patients before and after GH replacement. J Clin Endocrinol Metab 95:74–81

    Article  CAS  PubMed  Google Scholar 

  17. Prasad DS, Kabir Z, Dash AK, Das BC (2012) Prevalence and risk factors for metabolic syndrome in Asian Indians: a community study from urban Eastern India. J Cardiovasc Dis Res 3:204–211

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  18. Ravikiran M, Bhansali A, Ravi Kumar P, Bhansali S, Dutta P, Thakur JS, Sachdeva N, Bhadada S, Walia R (2010) Prevalence and risk factors of metabolic syndrome among Asian Indians: a community survey. Diabetes Res Clin Pract 89:181–188

    Article  PubMed  Google Scholar 

  19. Sawant A, Mankeshwar R, Shah S, Raghavan R, Dhongde G, Raje H, D’souza S, Subramanium A, Dhairyawan P, Todur S, Ashavaid TF (2011) Prevalence of metabolic syndrome in urban India. Cholesterol, Article ID 920–983

  20. Mc Johansen T, Richelsen B, Hansen HS, Din N, Malmlöf K (2003) Growth hormone-mediated breakdown of body fat: effects of GH on lipases in adipose tissue and skeletal muscle of old rats fed different diets. Horm Metab Res 35:243–250

    Article  Google Scholar 

  21. Kelestimur F, Jonsson P, Molvalilar S, Gomez JM, Auernhammer CJ, Colak R, Koltowska-Häggström M, Goth MI (2005) Sheehan’s syndrome: baseline characteristics and effect of 2 years of growth hormone replacement therapy in 91 patients in KIMS—Pfizer International Metabolic Database. Eur J Endocrinol 152:581–587

    Article  CAS  PubMed  Google Scholar 

  22. McConnell EM, Bell PM, Hadden DR, McCance DR, Sheridan B, Atkinson AB (2001) Prevalence of diabetes and impaired glucose tolerance in adult hypopituitarism on low dose oral hydrocortisone replacement therapy. Clin Endocrinal 54:593–599

    Article  CAS  Google Scholar 

  23. Lagrand WK, Visser CA, Hermens WT, Niessen HW, Verheugt FW, Wolbink JG, Hack CE (1999) C-reactive protein as a cardiovascular risk factor: more than an epiphenomenon? Circulation 100:96–102

    Article  CAS  PubMed  Google Scholar 

  24. Ridker PM, Hennekens CH, Buring JE, Rifai N (2000) C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. N Engl J Med 342:836–843

    Article  CAS  PubMed  Google Scholar 

  25. Mendall MA, Strachan DP, Butland BK, Ballam L, Morris J, Sweetnam PM, Elwood PC (2000) C-reactive protein: relation to total mortality, cardiovascular mortality and cardiovascular risk factors in men. Eur Heart 21:1584–1590

    Article  CAS  Google Scholar 

  26. Koenig W, Sund M, Fröhlich M, Fischer HG, Löwel H, Döring A, Hutchinson WL, Pepys MB (1999) C-Reactive protein, a sensitive marker of inflammation, predicts future risk of coronary heart disease in initially healthy middle-aged men: results from the MONICA (Monitoring Trends and Determinants in Cardiovascular Disease) Augsburg Cohort Study, 1984 to 1992. Circulation 99:237–242

    Article  CAS  PubMed  Google Scholar 

  27. Bollerslev J, Ueland T, Jørgensen AP, Fougner KJ, Wergeland R, Schreiner T, Burman P (2006) Positive effects of a physiological dose of GH on markers of atherogenesis: a placebo-controlled study in patients with adult-onset GH deficiency. Eur J Endocrinol 154:537–543

    Article  CAS  PubMed  Google Scholar 

  28. Gomez JM, Sahún M, Vila R, Domènech P, Catalina P, Soler J, Badimón L (2006) Peripheral fibrinolytic markers, soluble adhesion molecules, inflammatory cytokines and endothelial function in hypopituitary adults with growth hormone deficiency. Clin Endocrinol (Oxf) 64:632–639

    Article  CAS  Google Scholar 

  29. Auernhammer CJ, Strasburger CJ (1995) Effects of growth hormone and insulin-like growth factor I on the immune system. Eur J Endocrinol 133:635–645

    Article  CAS  PubMed  Google Scholar 

  30. Mohamed-Ali V, Goodrick S, Rawesh A, Katz DR, Miles JM, Yudkin JS, Klein S, Coppack SW (1997) Subcutaneous adipose tissue releases interleukin-6, but not tumor necrosis factor-alpha, in vivo. J Clin Endocrinol Metab 82:4196–4200

    CAS  PubMed  Google Scholar 

  31. Zhang J, Pugh TD, Stebler B, Ershler WB, Keller ET (1998) Orchiectomy increases bone marrow interleukin-6 levels in mice. Calcif Tissue Int 62:219–226

    Article  CAS  PubMed  Google Scholar 

  32. Blann AD, McCollum CN (1994) Circulating endothelial cell/leukocyte adhesion molecules in atherosclerosis. Thromb Haemost 72:151–154

    CAS  PubMed  Google Scholar 

  33. Porsch-Oezçueruemez M, Kunz D, Kloer HU, Luley C (1999) Evaluation of serum levels of solubilized adhesion molecules and cytokine receptors in coronary heart disease. J Am Coll Cardiol 34:1995–2001

    Article  PubMed  Google Scholar 

  34. Hung J, McQuillan BM, Chapman CM, Thompson PL, Beilby JP (2005) Elevated interleukin-18 levels are associated with the metabolic syndrome independent of obesity and insulin resistance. Arterioscler Thromb Vasc Biol 25:1268–1273

    Article  CAS  PubMed  Google Scholar 

  35. Elhadd TA, Abdu TA, Oxtoby J, Kennedy G, McLaren M, Neary R, Belch JJ, Clayton RN (2001) Biochemical and biophysical markers of endothelial dysfunction in adults with hypopituitarism and severe GH deficiency. J Clin Endocrinol Metab 86:4223–4232

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This study was wholly supported by Sher-I-Kashmir Institute of Medical Sciences (SKIMS), Soura, J&K, India and provided necessary Grant for the study.

Conflict of interests

None.

Author information

Authors and Affiliations

  1. Department of Endocrinology, Sher-I-Kashmir Institute of Medical Sciences, Soura, Srinagar, Jammu and Kashmir, India

    Manzoor Ahmad Bhat, Bashir Ahmad Laway, Arshad Iqbal Wani & Idrees Mubarik

  2. Department of Immunology, Sher-I-Kashmir Institute of Medical Sciences, Soura, Srinagar, Jammu and Kashmir, India

    Zaffar Amin Shah

Authors
  1. Manzoor Ahmad Bhat
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Bashir Ahmad Laway
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Zaffar Amin Shah
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Arshad Iqbal Wani
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Idrees Mubarik
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Bashir Ahmad Laway.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bhat, M.A., Laway, B.A., Shah, Z.A. et al. Insulin resistance, metabolic syndrome and chronic low grade inflammation in Sheehan’s syndrome on standard replacement therapy: a case control study. Pituitary 18, 312–318 (2015). https://doi.org/10.1007/s11102-014-0575-8

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11102-014-0575-8

Keywords

Search

Navigation